Based on the book The Great West That Was by William F. "Buffalo Bill" Cody, the film is about a cowboy named Buffalo Bill who goes up against a shady gambler who is attempting to scare off the townspeople so he can gain possession of a gold strike. When a nearby Indian tribe is provoked into attacking the town, the cavalry rides in to the rescue. Cody's book was also used as the inspiration for the studio's highly successful 1930 serial The Indians Are Coming.[1]Battling with Buffalo Bill was Universal Pictures's 78th serial, the 10th with sound and 4th with full sound, of the studio's total of 137 serials.

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The plot is a variation on the standard B-Western "Land Grab" plot: Gold has been discovered in the area and gambler Jim Rodney intends to make sole claim to it by pushing the rightful owners off the land and taking it for himself. To do so he has his henchmen kill an Indian woman, provoking attacks from her tribe. This brings Buffalo Bill and the United States Cavalry into the town. Buffalo Bill proceeds to defeat Rodney and his schemes.